FDA Likely to Approve H1N1 Vaccine In Advance of Data

GAITHERSBURG, Md., July 23 -- The FDA is likely to approve 2009 H1N1 (swine flu) vaccines before trial data can prove their safety and effectiveness against the virus.

Approving a vaccine without safety and immunogenicity data is not uncommon, FDA officials said during a daylong meeting of the Vaccines and Related Biological Products Advisory Committee.

The committee met to hear updates on H1N1 trials from the FDA, NIH, and the five companies that are applying for FDA approval of pandemic H1N1 vaccines.

In fact, the FDA approves seasonal influenza vaccines every year using its "strain change" process, in which it doesn't require vaccine manufacturers to provide safety and efficacy data.

What is different about how the FDA is likely to handle approval for a vaccine for pandemic H1N1, however, is that the agency doesn't normally approve vaccines while major clinical trials of safety and immunogenicity are ongoing.

Norman Baylor, PhD, director of FDA's Office of Vaccines Research and Review, explained the FDA's probable decision to go ahead with the simplified approval process, rather than a lengthy new drug application process.

"We have decades of experience with H1N1, that's why we feel we can do this with a strain-change," said Dr. Baylor.

Having a licensed vaccine doesn't mean that an immunization program will kick-off immediately -- that call has to come from the Secretary of Health and Human Services (HHS).

But given the prediction that H1N1 infection rates will pick up this fall, immunization programs are likely to begin before safety and immunological data collection is completed.

That trial data will begin trickling in during August and continue through early 2010.

The World Health Organization (WHO) and the NIH have said they want to start vaccinating people by mid-October.

Of the five companies applying for FDA approval -- Novartis, sanofi pasteur, CSL Biotherapies, GlaxoSmithKline, and MedImmune -- only CSL has already started human trials. The Australian company, which provides seasonal flu vaccines to the U.S., inoculated its first human trial participant Wednesday.

Meanwhile, the NIH announced it was set to begin clinical trials in the United States of vaccines made by sanofi-pasteur and CSL.

Because an immunization program will likely run at the same time as the trial, the FDA said it would issue updates as the trials answer key questions. They include whether two shots are better than one, and how the vaccine interacts with seasonal flu shots.

"That's the harder decision -- how those immunization decisions will be made as that data comes in," said Dr. Baylor.

There's a chance the early data will show the vaccine is ineffective at stimulating an immune response. If that's the case, the FDA might have to issue an "emergency use authorization" for an oil-in-water adjuvant that sparks a stronger reaction in the immune system, but causes more side effects.

There are currently no licensed influenza vaccines that contain an adjuvant, and Dr. Baylor said he couldn't recall a time when the FDA issued an emergency use authorization for a vaccine.

Two companies, GlaxoSmithKline and Novartis, are applying for approval for vaccines that contain oil-in-water adjuvants. The NIH is also conducting a trial of an adjuvant-enhanced vaccine.

The panel's consumer representative said if the FDA does issue an emergency use authorization for a adjuvanted vaccine, she would prefer as little adjuvant as possible to avoid side effects.

Another panelist, Theodore Eickhoff, MD, an infectious disease specialist at the University of Colorado, said adjuvanted flu vaccines have been used for a decade in Europe and have not been shown to harm vulnerable populations, such as children.

The government has already purchased a supply of 120 million adjuvant doses that it will add to its antigen supply if it there is a shortage of the vaccine, or if the standard versions are shown to be ineffective.

The panel did not reach consensus on whether patients should receive one or two doses. Once trial data becomes available, it will be more apparent whether doses given 21 days apart are superior to a single dose, members indicated.

The committee agreed that pregnant women should be immunized, but did not recommend inoculation of babies under six months old.

The chairman of the committee, a pediatrician, said the FDA might want to prepare for an infant vaccination program if surveillance data indicate a wider pandemic than expected.

"I don't think it would be a bad idea to have a game plan to immunize babies under six months in case of emergency," said John Modlin, MD, a pediatrician at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

FDA officials also told the panel that vaccine manufactures are getting only one-third as much antigen from the pandemic H1N1 strain as they normally get from the seasonal flu virus. That might mean vaccine makers won't be able to make as many doses as they planned.

The CDC's Advisory Committee on Immunization Practices will meet in Atlanta next week to vote on which populations should be vaccinated first, among other issues.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine

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